Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks
Summary: Replication of a damaged DNA template can threaten the integrity of the genome, requiring the use of various mechanisms to tolerate DNA lesions. The Smc5/6 complex, together with the Nse2/Mms21 SUMO ligase, plays essential roles in genome stability through undefined tasks at damaged replica...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719314561 |
| _version_ | 1818254491620737024 |
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| author | Mariel Zapatka Irene Pociño-Merino Hayat Heluani-Gahete Marcelino Bermúdez-López Marc Tarrés Eva Ibars Roger Solé-Soler Pilar Gutiérrez-Escribano Sonia Apostolova Celia Casas Luis Aragon Ralf Wellinger Neus Colomina Jordi Torres-Rosell |
| author_facet | Mariel Zapatka Irene Pociño-Merino Hayat Heluani-Gahete Marcelino Bermúdez-López Marc Tarrés Eva Ibars Roger Solé-Soler Pilar Gutiérrez-Escribano Sonia Apostolova Celia Casas Luis Aragon Ralf Wellinger Neus Colomina Jordi Torres-Rosell |
| author_sort | Mariel Zapatka |
| collection | DOAJ |
| description | Summary: Replication of a damaged DNA template can threaten the integrity of the genome, requiring the use of various mechanisms to tolerate DNA lesions. The Smc5/6 complex, together with the Nse2/Mms21 SUMO ligase, plays essential roles in genome stability through undefined tasks at damaged replication forks. Various subunits within the Smc5/6 complex are substrates of Nse2, but we currently do not know the role of these modifications. Here we show that sumoylation of Smc5 is targeted to its coiled-coil domain, is upregulated by replication fork damage, and participates in bypass of DNA lesions. smc5-KR mutant cells display defects in formation of sister chromatid junctions and higher translesion synthesis. Also, we provide evidence indicating that Smc5 sumoylation modulates Mph1-dependent fork regression, acting synergistically with other pathways to promote chromosome disjunction. We propose that sumoylation of Smc5 enhances physical remodeling of damaged forks, avoiding the use of a more mutagenic tolerance pathway. : Zapatka et al. show that sumoylation of Smc5 helps cells tolerate DNA lesions at damaged replication forks in an error-free mode. Using unsumoylatable smc5-KR mutants, they show that this modification operates through Mph1 in fork regression, working in parallel with several nucleases and helicases to promote chromosome segregation. Keywords: Smc5, Nse2, Mms21, SUMO, Mph1, DNA damage tolerance, fork regression, DNA replication, yeast, chromosome |
| first_indexed | 2024-12-12T16:56:49Z |
| format | Article |
| id | doaj.art-e4baae4489f34545a1af31aa85bcf453 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T16:56:49Z |
| publishDate | 2019-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-e4baae4489f34545a1af31aa85bcf4532022-12-22T00:18:13ZengElsevierCell Reports2211-12472019-12-01291031603172.e4Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication ForksMariel Zapatka0Irene Pociño-Merino1Hayat Heluani-Gahete2Marcelino Bermúdez-López3Marc Tarrés4Eva Ibars5Roger Solé-Soler6Pilar Gutiérrez-Escribano7Sonia Apostolova8Celia Casas9Luis Aragon10Ralf Wellinger11Neus Colomina12Jordi Torres-Rosell13Departament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, SpainDepartament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, SpainCABIMER-Universidad de Sevilla, Avenida Americo Vespucio sn, 41092 Sevilla, SpainDepartament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, SpainDepartament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, SpainDepartament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, SpainDepartament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, SpainMRC London Institute of Medical Sciences, Du Cane Road, London W12 0NN, UKDepartament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, SpainDepartament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, SpainMRC London Institute of Medical Sciences, Du Cane Road, London W12 0NN, UKCABIMER-Universidad de Sevilla, Avenida Americo Vespucio sn, 41092 Sevilla, SpainDepartament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, SpainDepartament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, 25198 Lleida, Spain; Corresponding authorSummary: Replication of a damaged DNA template can threaten the integrity of the genome, requiring the use of various mechanisms to tolerate DNA lesions. The Smc5/6 complex, together with the Nse2/Mms21 SUMO ligase, plays essential roles in genome stability through undefined tasks at damaged replication forks. Various subunits within the Smc5/6 complex are substrates of Nse2, but we currently do not know the role of these modifications. Here we show that sumoylation of Smc5 is targeted to its coiled-coil domain, is upregulated by replication fork damage, and participates in bypass of DNA lesions. smc5-KR mutant cells display defects in formation of sister chromatid junctions and higher translesion synthesis. Also, we provide evidence indicating that Smc5 sumoylation modulates Mph1-dependent fork regression, acting synergistically with other pathways to promote chromosome disjunction. We propose that sumoylation of Smc5 enhances physical remodeling of damaged forks, avoiding the use of a more mutagenic tolerance pathway. : Zapatka et al. show that sumoylation of Smc5 helps cells tolerate DNA lesions at damaged replication forks in an error-free mode. Using unsumoylatable smc5-KR mutants, they show that this modification operates through Mph1 in fork regression, working in parallel with several nucleases and helicases to promote chromosome segregation. Keywords: Smc5, Nse2, Mms21, SUMO, Mph1, DNA damage tolerance, fork regression, DNA replication, yeast, chromosomehttp://www.sciencedirect.com/science/article/pii/S2211124719314561 |
| spellingShingle | Mariel Zapatka Irene Pociño-Merino Hayat Heluani-Gahete Marcelino Bermúdez-López Marc Tarrés Eva Ibars Roger Solé-Soler Pilar Gutiérrez-Escribano Sonia Apostolova Celia Casas Luis Aragon Ralf Wellinger Neus Colomina Jordi Torres-Rosell Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks Cell Reports |
| title | Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks |
| title_full | Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks |
| title_fullStr | Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks |
| title_full_unstemmed | Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks |
| title_short | Sumoylation of Smc5 Promotes Error-free Bypass at Damaged Replication Forks |
| title_sort | sumoylation of smc5 promotes error free bypass at damaged replication forks |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719314561 |
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